Risk of Preeclampsia and Other Pregnancy Complications in Frozen Single Euploid Embryo Transfers After Natural Versus Artificial Endometrial Preparation: A Truncated Randomized Controlled Trial

Introduction: To determine for the first time the incidence of preeclampsia and other pregnancy complications according to the mode of endometrial preparation for frozen embryo transfer (FET) in a randomized fashion.

Methods: Women about to undergo FET of a single euploid blastocyst were randomly assigned to a modified natural cycle (MNC) or an artificial cycle (AC). Inclusion criteria were as follows: Caucasian; non-obese; 18-43 years of age; nulliparity; regular menstrual cycles; and autologous oocytes. Exclusion criteria were as follows: uterine alterations; moderate-heavy smokers; gamete donation; and chronic diseases. A pilot sub-study of first-trimester markers of preeclampsia was performed in 60 of the patients.

Results: Of the 1260 patients estimated, 591 met the inclusion criteria and were willing to participate; of these, 306 and 285 were randomly assigned to a MNC or AC, respectively. After exclusion, 242 and 227 patients finally underwent a MNC or AC, resulting in 131 and 103 clinical pregnancies, 121 and 92 live births, and 91 and 70 questionnaires obtained concerning pregnancy complications, respectively. The incidence of preeclampsia was double in the AC group (10.00 % versus 4.39 %), though not significantly different. In the AC group, the prevalence of first trimester bleeding was significantly higher (42.85 % versus 15.38 %), and there was a significant reduction in live birth rates (40.53 % versus 50.00 %) in the per protocol analysis. No differences in early markers of preeclampsia were detected between the two groups.

Discussion: Although this randomized study was truncated, our findings are in accordance with previous reports of a higher risk of preeclampsia and other complications when the endometrium is artificially prepared for FET.